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FLASH GENE

Symbol

SH3BP2

contributors: mct/npt - updated : 04-11-2015

HGNC name	SH3-domain binding protein 2
HGNC id	10825

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CRBM cherubism
Location	4p16.3      Physical location : 2.794.749 - 2.842.822
Synonym name	cherubism
	Abl-SH3 binding protein 2
	TNFAIP3 interacting protein 2
Synonym symbol(s)	RES4.23, 3BP2, CRBM, CRPM, FLJ42079

DNA

TYPE	functioning gene
STRUCTURE	48.07 kb     13 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
	Binding site
text structure	basal promoter of SH3BP2 is located between &
	8722;200 and +86 from the transcription start site (TSS)
	SH3BP2 TSS is located in exon IB, not exon IA in human tissue
	lacks a TATA box
	three GC-boxes in the promoter/regulatory region
	PARP1 was able to bind to the SH3BP2 promoter

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	exon 1B falls within the exons of a bone-expressed gene strongly predicted to translate 561 amino acids protein named SH3BP2 (PMID: 22820184)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003023 13 - 9209 NP_003014 - 561 - 2012 22820184 NM_001122681 13 - 9068 NP_001116153 - 561 - 2012 22820184 NM_001145855 13 - 9211 NP_001139327 - 589 - 2012 22820184 NM_001145856 13 - 9158 NP_001139328 - 618 - 2012 22820184

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Endocrine pancreas         Lymphoid/Immune spleen       highly Nervous brain           nerve       highly Respiratory lung           respiratory tract larynx

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Homo sapiens Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Homo sapiens not specific mast cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal pleckstrin homology (PH) domain
	a ten AA SH3 binding domain
	three modular pepetide recognition domains
	a proline-rich stretch that binds to Src homology (SH) 3 domain-containing proteins
	a C terminal SH2 domain

HOMOLOGY

interspecies

homolog to murine Sh3bp2

Homologene

FAMILY

CATEGORY

adaptor , regulatory , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
text	cytoplasmic adaptor protein mainly expressed by hematopoietic cells

basic FUNCTION	involved in setting tresholds for the increased osteoclast and osteoblast activities essential for normal tooth eruption
	participates in a phosphatidyl-inositol specific phospholipase C (PI-PLC), inositol phosphate-3 receptor (IP3R), and calcineurin dependent signaling cascade that activates calcineurin-induced nuclear translocation of NFATC1, leading to increased differentiation of TRAP-positive osteoclastic cells
	regulates immune receptor-mediated signal transduction
	role for the SH3BP2 adapter protein in osteoblast function and in coordinating bone homeostatic signals in both osteoclast and osteoblast lineages
	is required for G protein-coupled receptor-mediated neutrophil functions
	obligate requirement for SH3BP2 in G protein-coupled receptor-mediated neutrophil function
	plays a role in osteoclastogenesis
	is an important regulator of cytotoxic granule release in NK cells
	by participating in FCER1A- mediated signal transduction SH3BP2 is an important regulator of human mast cells activation
	playing an unexpected role in endocytic and cytoskeletal regulation through its interaction with SH3KBP1 and DBNL
	SH3BP2 is a key regulator for TNF-induced osteoclastogenesis
	cytoplasmic adaptor protein that acts as a positive regulator in mast cell FCER1A-dependent signaling
	regulates human mast cells (huMCs) survival and participates in KIT-mediated signal transduction by directly controlling KIT receptor expression

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	SH3 binding with ABL oncogene (negative regulation of ABL)
	induces the protein complex with cellular signaling molecules through phosphorylation of Tyr(183) and SH2 domain leading to the activation of NFATC1 in B cells
	PTPN6 inducibly interacts with the SH2 domain of SH3BP2 after the aggregation of FCER1A (directly interacts with Tyr(564) -phosphorylated form of PTPN6 and positively regulates the function of PTPN6 in FCER1A-mediated signaling in mast cells)
	TNKS regulates SH3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts
	endogenous SH3BP2 ubiquitylation is stimulated by TNKS2 and requires PARP activity
	RNF146 is the functional E3-ligase controlling SH3BP2 protein levels
	PARP1 can interact with a cis-DNA element in the SH3BP2 promoter/regulatory region and regulates the expression of SH3BP2

cell & other

REGULATION

Other

PARP1 regulates expression of SH3BP2

ASSOCIATED DISORDERS

corresponding disease(s)

CRBM

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in bladder carcinoma constitutional     --over   was sufficient to induce osteoclast formation (even in the absence of RANKL) and elevated TNF secretion in macrophages, two critical features of the cherubism phenotype

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology inflammatory   therapeutic target in mast cell-mediated inflammatory diseases and deregulated KIT disorders osteoarticular bone   is a potential target for suppression of pathologic bone resorption

ANIMAL & CELL MODELS

Sh3bp2-/- mice developed osteoporosis as a result of reduced bone formation despite the fact that bone resorption was impaired